The present invention relates to the treatment of matrix mineralization disorders such as hypophosphatasia (HPP). HPP is a rare, heritable disease caused by one or more loss-of-function mutation in the gene ALPL, which encodes tissue-nonspecific alkaline phosphatase (TNALP; a.k.a liver/bone/kidney type ALP). Alkaline phosphatase deficiency in osteoblasts and chondrocytes impairs skeletal mineralization, leading to rickets or osteomalacia. The severity of HPP depends on its age of onset. Perinatal HPP, the most severe form of HPP, results in an almost complete absence of bone mineralization in utero and can cause stillbirth. Infantile HPP, diagnosed before the age of six months, results in impaired skeletal mineralization that can lead to fractures and deformities. Childhood HPP can cause the premature loss of deciduous teeth and rickets. Finally, adult HPP can cause stress fractures and attacks of arthritis and pyrophosphate arthropathy.
Given the devastating immediate and long-term impact of matrix mineralization disorders such as HPP on affected patients, particularly infants and children, there is a need to develop methods and compositions for treating matrix mineralization disorders.